THE EFFECTS OF CYPROTERONE ACETATE AND ETHINYL OESTRADIOL ON CARBOHYDRATE METABOLISM

Abstract

Carbohydrate metabolism was studied in a group of 66 women, taking cyproterone acetate (CA) and ethinyloestradiol (EO) as antiandrogen therapy for the treatment of hirsutism and/or acne. A reverse sequential treatment cycle was used and the women were studied in 2 groups: the 1st when taking the combination of CA and EO during the first 12 days of the treatment cycle, and the second taking EO alone during days 13-22. The combination reduced fasting plasma glucose and raised fasting plasma insulin concentrations. There was deterioration of glucose tolerance with increased plasma insulin concentrations and these effects were progressive with time. The plasma insulin response to i.v. tolbutamide was increased by 50%, but there was no accompanying change in the glucose nadir as compared with controls. Thus, the combination of CA and EO causes insulin resistance. Plasma C-peptide concentrations following oral glucose were unchanged compared with controls. The observed hyperinsulinemia was due to a reduction of hepatic uptake of insulin rather than its increased secretion. Apparently these effects are due to a CA-induced elevation of fasting plasma insulin resulting in downregulation of hepatic insulin receptors with subsequent induction of insulin resistance and impairment of hepatic insulin uptake. C-peptide concentrations following i.v. tolbutamide were significantly higher on treatment with CA and EO than in controls indicating increased pancreatic secretion of insulin. Tests carried out while patients were taking EO alone showed impairment of glucose tolerance only with no change in insulin levels. There was an increase in plasma insulin in response to tolbutamide, but this was not significant. These results are explained by a reduced, but persisting effect of CA.